In the existing process for preparing the above compound of formula (1), an optically active 3-hydroxyester compound was reacted with lithium enolate of t-butylacetate generated by the treatment of lithium diisopropylamide (LDA) or lithium hexamethyldisilazide (LHMDS) at low temperature (−78° C.) to provide compound of formula (1) (see: U.S. Pat. No. 5,278,313). Recently, a similar reaction to the above was successfully carried out by the addition of Grignard reagent before Claisen condensation. This condition enabled the reaction performed at 5° C. (see: European Patent Laid-open Publication No. 1104750).
The above processes, however, used excess lithium hexamethyldisilazide or lithium diisopropylamide that has some problems to be used in the industrial production. Moreover, the former route is complicated by the formation of significant amount of undesired side products even at very low temperature (see: Tetraehdron Lett., 2002, 43, 2679–2682). The latter precedent results in pretty low yield comparing to the former process. The only advantage of the latter process is that the reaction can be executed at 5° C.